Physiological challenges and metabolic adaptations during human fetal development and at delivery

Abstract

Demographic shifts, shaped by social and biological factors, highlight the need to improve pregnancy care and early childhood interventions to achieve lasting health benefits. From zygote attachment to birth, the synchronized physiological and metabolic changes in embryonic and fetal growth and maternal-fetal nutrition ensure that oxygen availability meets the energy needs of the developing fetus. Key factors include fetal hemoglobin facilitating maternal-to-fetal oxygen delivery, hormones like human chorionic gonadotropin regulating placental formation, and the hypoxia-inducible factor serving as a mechanism for fetal adaptation to low oxygen while enhancing glucose metabolism. Additionally, changes in fetal temperature, blood flow, and pH relative to the mother act as physiological mechanisms, improving oxygen delivery from the fetal bloodstream to tissues. At birth, the newborn undergoes profound respiratory, cardiovascular, and metabolic adjustments to adapt to the extra-uterine life environment. In this review, we explore the primary physiological and metabolic mechanisms enabling the human embryo and fetus to thrive and grow despite the critical constraints faced throughout its development and at the time of delivery. We discuss how metabolic changes ensure immediate survival and influence long-term health and their potential to prevent non-communicable chronic diseases. Enhancing our understanding of these critical physiological and metabolic changes during development can guide interventions for optimizing fetal growth, development, and long-term human health.